Overview of recently approved 505(b)(2) new drug applications (2010-2012): role of clinical pharmacology.

The role of clinical pharmacology (CP) in the approval of 505(b)(2) NDAs was explored with the goal of sharing with the drug development community, some of the critical CP aspects that need to be considered and addressed during the planning and submission of a 505(b)(2) NDA. Among the 106 505(b)(2) NDAs approved in 2010-2012 (excluding those that were approved under the PEPFAR program), 25% included only CP information, no supportive clinical safety/efficacy was necessary for their approval and 43% included both clinical and CP information. A review of the pre-submission interaction discussion held for 58% of the non-PEPFAR NDAs, indicated that CP-related aspects discussed at this avenue included study design of the pivotal BA/BE study, biowaiver related discussion, need for additional or supportive pharmacokinetic information to be included in the NDA, selection of the most appropriate reference drug product for 505(b)(2) purpose, as well as acceptability of publicly available information to address data gaps in knowledge. Further, we also noted that 505(b)(2) NDAs that did not report having a pre-submission interaction with the Agency had twice the rate of receiving a complete response action in the first cycle as compared to the NDAs that did meet with the Agency.